Birth Control Pills May Produce Protracted Effects on Testosterone Levels

Action Points

Inform patients who ask taking oral contraceptives that use of birth control pills has been associated in a small retrospective study with elevated sex hormone-binding globulin levels and reduced bioavailable testosterone. This effect may persist even after discontinuation of oral contraceptive use.

A larger prospective study would be needed to determine the long-term effects of these findings.

A analysis of blood samples showed that women who had discontinued taking birth control pills six months earlier showed sex hormone-binding globulin levels that were almost double than levels seen in women with no history of OC use (P<0.0001), found Claudia Panzer, M.D., of Boston University and colleagues.

Women currently taking birth control pills had even higher levels, the BU group reported in the January issue of The Journal of Sexual Medicine. Their sex hormone-binding globulin levels were four times higher than those seen in women with no OC exposure (P<0.0001).

The researchers said they expected the current pill users to have higher sex hormone-binding globulin levels than the non-users, but they were surprised to see that the discontinued users still had higher-than-normal levels. The effect persisted even for women who used transdermal testosterone replacement therapy during the study.

Both the acute and lasting effects of oral contraceptive use on sex hormone-binding globulin levels, which binds to testosterone, suggests that women exposed to birth control pills may have reduced bioavailable testosterone and therefore be at risk for sexual problems, the authors said. The study did not measure whether the effects are ultimately reversible.

Dr. Panzer and colleagues said lowered levels of bioavailable or free testosterone-believed to play a major role in women's sexual health-could place women at risk for decreased sexual desire, arousal, decreased lubrication and increased sexual pain.

In the retrospective study, Dr. Panzer and colleagues compared 62 current birth control users with 39 discontinued users and 23 women who had never used the pills. All of the women were premenopausal and their mean ages were 32, 33, and 36, respectively. All of the participants had reported sexual dysfunction for at least six months.

All patients were offered the opportunity to use transdermal testosterone therapy to improve their sexual function. The treatment was a testosterone gel applied daily, typically at 10% of the amount prescribed for men.

Sex hormone-binding globulin levels were measured at four points during the study, at baseline, while using oral contraceptives, at a mean of 80 days after discontinued use, and then again at about 120 days after discontinuation.

The discontinued pill users showed a significant drop in sex hormone-binding levels at follow-up, but they were still quite higher than non-users, 64 nmol/L Â± 4 versus 35 nmol/L Â± 4, respectively. Current user's levels remained unchanged, measuring 149 nmol/L Â± 10 at a mean of 132 days after baseline.

Eleven women who had discontinued use were followed for about one year and even after a mean of 11.3 months since they had stopped taking birth control pills, their sex hormone-binding globulin levels measured 73 nmol/L Â± 6, the researchers reported.

These observations were surprising, the authors said, "as the effect of oral contraceptives on sex hormone-binding globulin levels should have subsided." The findings are even more interesting, Dr. Panzer and her team noted, because these women also received transdermal testosterone therapy, which should have decreased sex hormone-binding globulin levels.

Not surprisingly, bioavailable testosterone levels were significantly higher for women who had never used birth control pills. Current birth control users and discontinued users both showed similar reduced levels of bioavailable testosterone, 165.2 pmol/L Â± 17.7 and 165.9 pmol/L Â± 16.7, respectively, whereas the women with no oral contraceptive exposure had significantly higher levels measuring 508.4 pmol/L Â± 76. 3, P<0.0001.

Dr. Panzer and colleagues noted that earlier research has shown increases in sex hormone-binding globulin levels with oral contraceptive use to be associated with a concomitant 40% to 60% decrease in free testosterone levels.

The investigators suggested that prolonged exposure to the synthetic estrogens found in oral contraceptives may trigger permanent changes in gene expression that leads to the elevated levels of sex hormone-binding globulin.

The authors cautioned that their study sample is small and that the participants took a variety of oral contraceptives for various lengths of time. It is not known then whether there is a dose-response relationship.

However, on the basis of these results, the researchers suggested that the next step should be whether a longer study would allow for a reversal of these effects.

"Further research is needed to identify whether sex hormone-binding globulin changes induced by oral contraceptives may or may not be completely reversible after discontinuation of oral contraceptive use and whether this leads to long-term sexual, metabolic, and mental health changes in women," they concluded.

Reviewed by Zalman S. Agus, MD Emeritus Professor at the University of Pennsylvania School of Medicine

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